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PLoS One. 2013 Oct 10;8(10):e75297. doi: 10.1371/journal.pone.0075297. eCollection 2013.

Snapin, positive regulator of stimulation- induced Ca²⁺ release through RyR, is necessary for HIV-1 replication in T cells.

Author information

1
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America ; Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, Suita, Osaka, Japan.

Abstract

To identify critical host factors necessary for human immunodeficiency virus 1 (HIV-1) replication, large libraries of short-peptide-aptamers were expressed retrovirally. The target of one inhibitor peptide, Pep80, identified in this screen was determined to be Snapin, a protein associated with the soluble N-ethyl maleimide sensitive factor adaptor protein receptor (SNARE) complex that is critical for calcium-dependent exocytosis during neurotransmission. Pep80 inhibited Ca²⁺ release from intracellular stores and blocked downstream signaling by direct interruption of the association between Snapin and an intracellular calcium release channel, the ryanodine receptor (RyR). NFAT signaling was preferentially abolished by Pep80. Expression of Snapin overcame Pep80-mediated inhibition of Ca²⁺/NFAT signaling and HIV-1 replication. Furthermore, Snapin induced HIV-1 replication in primary CD4⁺ T cells. Thus, through its interaction with RyR, Snapin is a critical regulator of Ca²⁺ signaling and T cell activation. Use of the genetically selected intracellular aptamer inhibitors allowed us to define unique mechanisms important to HIV-1 replication and T cell biology.

PMID:
24130701
PMCID:
PMC3794929
DOI:
10.1371/journal.pone.0075297
[Indexed for MEDLINE]
Free PMC Article

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